Epcoritamab R-CHOP DLBCL combination cuts progression risk 51% in Phase 3

The epcoritamab R-CHOP DLBCL trial produced the first statistically significant progression-free survival benefit for a bispecific antibody combination in frontline treatment. In EPCORE DLBCL-2, the risk of progression or death fell by 51% in adults with newly diagnosed diffuse large B-cell lymphoma compared with R-CHOP alone. Genmab and AbbVie released the topline findings on 5 October 2026.

The hazard ratio was 0.49 (95% CI 0.36, 0.67; p < 0.0001) in patients with an International Prognostic Index score of 2 to 5. Epcoritamab was given as a fixed-duration, subcutaneous regimen with standard-of-care R-CHOP, which combines rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine and prednisone. Genmab and AbbVie reported that the safety profile of the combination was generally well tolerated and matched the profiles previously reported for each agent alone.

What the epcoritamab R-CHOP DLBCL result shows

Source: Genmab company announcement no. 40, 5 October 2026

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The primary endpoint measured progression-free survival in participants with an IPI score of 3 to 5. The key secondary endpoint measured progression-free survival across all participants with an IPI score of 2 to 5. Both populations showed the same hazard ratio of 0.49. The announcement covers progression-free survival only.

A first for bispecific combinations in first-line treatment

“These topline results of epcoritamab in combination with R-CHOP mark the first Phase 3 study to demonstrate a statistically significant improvement in progression-free survival in patients with newly diagnosed DLBCL treated with a bispecific antibody combination and have the potential to reshape the frontline treatment landscape,” said Jan van de Winkel, chief executive officer of Genmab. “While treatment advances have improved outcomes for patients with diffuse large B-cell lymphoma, options for newly diagnosed patients remain limited, reinforcing the need for additional therapies that can treat as many patients as possible in the frontline setting.”

Daejin Abidoye, vice president and therapeutic area head for oncology, solid tumor and hematology at AbbVie, said the topline results “suggest that epcoritamab combined with R-CHOP could offer a potential new standard of care in newly diagnosed DLBCL patients”, adding that the findings strengthen the companies’ understanding of bispecifics across lymphoma treatment.

Gilles Salles, chief of the lymphoma service at Memorial Sloan Kettering Cancer Center, noted that he took part in both the landmark trial that established R-CHOP as a standard of care close to 25 years ago and in EPCORE DLBCL-2. “The 51% reduction in the risk of progression or death is clinically meaningful and highly relevant to everyday practice,” he said. “These results have the potential to be practice-changing and could mark an important step forward in bringing the opportunity of cure to more patients.”

Why the DLBCL first-line setting matters

Diffuse large B-cell lymphoma is the most common non-Hodgkin lymphoma worldwide, accounting for around 25 to 30 percent of all NHL cases, with roughly 25,000 new diagnoses each year in the US. It is more common in older adults and slightly more prevalent in men, and it can arise in lymph nodes or in organs outside the lymphatic system. It grows quickly, and many patients relapse after treatment or have disease that does not respond to it, so management remains difficult despite the therapies introduced since R-CHOP was established.

R-CHOP has anchored first-line treatment since the landmark trial that set it as a standard of care close to 25 years ago, which is why a positive Phase 3 readout on the backbone itself carries weight. A subcutaneous, fixed-duration regimen also changes how treatment is delivered, since the trial schedule ends after eight cycles of therapy rather than continuing until progression.

Source: Genmab company announcement no. 40, 5 October 2026